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EXPERIMENTAL STUDIES

Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism

^a Cardiac Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, London, United Kingdom
^* Department of Physiology, University of Sydney, Sydney, Australia

Manuscript received December 30, 1998; revised manuscript received December 30, 1999, accepted February 21, 2000.

Reprint requests and correspondence: Dr. Peter Collins, Cardiac Medicine, Imperial College School of Medicine at the National Heart & Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom
peter.collins{at}ic.ac.uk

OBJECTIVES

To investigate the potential for plant derived estrogens (phytoestrogens) genistein, phloretin, biochanin A and zearalanone to relax rabbit coronary arteries in vitro and to determine the mechanism(s) of such relaxation.

BACKGROUND

Epidemiological data suggests a reduction in the incidence of coronary heart disease in humans who have a high intake of phytoestrogens.

METHODS

Isolated rabbit coronary artery rings were suspended in individual organ baths, precontracted with potassium chloride (30mM), and the relaxing effects and mechanisms of relaxation to genistein, phloretin, biochanin A and zearalanone were determined by measurement of isometric tension.

RESULTS

Genistein, phloretin and biochanin A induced significant gender-independent relaxation in rings with and without endothelium. Inhibition of nitric oxide and prostaglandin synthesis with L-NAME and indomethacin had no effect on genistein-induced relaxation. Relaxation was unaffected by the specific estrogen receptor antagonist ICI 182,780, the ATP-sensitive potassium channel inhibitor glibenclamide and the potassium channel inhibitor, barium chloride. Calcium concentration-dependent contraction curves in high potassium depolarization medium were significantly shifted to the right and downward after incubation with genistein and zearalanone. An inhibitory effect of genistein (2 µM) on L-type calcium current in guinea-pig ventricular myocytes confirmed a calcium antagonist relaxing mechanism of action. In healthy volunteers, plasma genistein levels of approximately 2 µM are achieved after ingestion of a commercially available soy protein drink (Supro) containing 37 mg genistein.

CONCLUSIONS

This study demonstrates that phytoestrogens induce endothelium-independent relaxation of coronary arteries; the mechanism involves calcium antagonism. These mechanisms may contribute to the potential long-term cardiovascular protective effect of these substances.

Abbreviations and Acronyms   ACh = acetylcholine   HEPES = hydroxyethyl pipirazine-ethanesulphonic acid   ICa = L-type calcium current   L-NAME = Nomega-nitro-L-arginine methyl ester

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